Aminopeptidase



Aminopeptidases (AP) are metal - mostly Zn-dependent enzymes involved in the digestion of proteins. Cytosol AP (Cyt-AP), deblocking AP (DAP) and AP N (APN) remove N-terminal amino acids. The AP are classified by the amino acid which they hydrolyze. Other types of AP are: Cold-activated AP (Col-AP), Heat stable AP from Thermus thermophilus (AmpT), AP from Staphylococcus aureus (AmpS) and SGAP from Stereomyces griseus. Aminopeptidases catalyze a release of an N-terminal amino acid from a peptide, amide, or arylamide. The images at the left and at the right correspond to one representative Aminopeptidase, i.e. the crystal structure of Stereomyces griesus aminopeptidase (1xjo).

3D Structures of Aminopeptidase
Update June 2011

Cysteine aminopeptidase
3pw3 – Cys-AP – Parabacteroides distasonis

Glutamic acid aminopeptidase
2wyr – PhGlu-AP+Co – Pyrococcus horikoshii

3kl9 – Glu-AP – Streptococcus pneumoniae

Alanine aminopeptidase
3ebg – PfAla-AP - Plasmodium falciparum

3ebh - PfAla-AP+bestatin

3ebi - PfAla-AP+dipeptide analog

Proline aminopeptidase
3ovk – Xaa Pro-AP – Streptococcus pyogenes

3il0 - Xaa Pro-AP – Streptococcus thermophilus

2v3x, 2v3y, 2v3z - Xaa EcPro-AP (mutant)+tripeptide

1w7v, 2bh3 - Xaa EcPro-AP+Zn+Mg+polypeptide

2bn7 - Xaa EcPro-AP+Zn+Mg+Mn+polypeptide

2bha, 2bhd - Xaa EcPro-AP+Mg+polypeptide

1a16 - Xaa EcPro-AP+Mn+polypeptide

1wbq, 2bhb - Xaa EcPro-AP+Zn+Mg

2bhc - Xaa EcPro-AP+Na+Mg

1wl6 - Xaa EcPro-AP+Mg

1wi9, 1m35, 1jaw - Xaa EcPro-AP+Mn

1wlr - Xaa EcPro-AP

2bws, 2bwt, 2bwu, 2bwv, 2bww, 2bwx, 2bwy - Xaa EcPro-AP (mutant)

1w2m - Xaa EcPro-AP+Ca

1n51 – Xaa EcPro-AP+apstatin

2zsg – X TmPro-AP – Thermatoga maritime

3ctz – X hPro-AP – human

1x2b, 1x2e, 1wm1 – SmPro-AP + inhibitor – Serratia marcescens

1qtr – SmPro-AP

1xqv – TaPro-AP (mutant) – Thermoplasma acidophilum

1xqw, 1xqx, 1xqy, 1xrl, 1xrm, 1xrn, 1xro, 1xrp, 1xrq, 1xrr – TaPro-AP+polypeptide

Leucine aminopeptidase
3jru – Leu-AP – Xanthomonas oryzae

2hc9, 2hb6 – Leu-AP – Caenorhabditis elegans

2ewb – bLeu-AP+zofenoprilat – bovine

1lam, 1lap – bLue-AP

1bpm, 1bpn – bLue-AP+Zn+Mg

1lan, 1lcp – bLue-AP+leucine derivative

1bll – bLue-AP+amastatin

2xdt, 2yd0 – hLeu-AP soluble domain

3mdj - hLeu-AP soluble domain + inhibitor

3h8e, 3h8f, 3h8g – Leu-AP – Pseudomonas putida

3kqx, 3kqz, 3kr4, 3kr5 – PfLeu-AP

3fh4, 1rtq, 2dea – VpLeu-AP – Vibrio proteolyticus

3b35, 3b3t, 3b3v, 2anp - VpLeu-AP (mutant)

3b3c, 3b3s, 3b3w - VpLeu-AP (mutant)+Leu derivative

3b7i - VpLeu-AP (mutant)+Leu

1ft7 - VpLeu-AP +Leu derivative

2nyq, 2iq6 – VpLeu-AP+polypeptide

1lok – VpLeu-AP+Tris

2prq – VpLeu-AP+Co

1xry, 1txr – VpLeu-AP+bestatin

1gyt – EcLeu-AP

3qnf – hLeu-AP 1

Methionine aminopeptidase
3mr1, 3mx6 – Met-AP+Mn – Rickettsia prowazekii

2dfi, 1xgm, 1xgn, 1xgo, 1xgs – PfMet-AP+Co – Pyrococcus furiosus

1wkm - PfMet-AP+Mn

3iu7 – MtMet-AP+Mn +A02 – Mycobacterium tuberculosis

3iu8, 3iu9 - MtMet-AP+Ni + inhibitor

1yj3 - MtMet-AP+Co

3pka - MtMet-AP+Mn

3pkb, 3pkc, 3pkd, 3pke - MtMet-AP+bengamide inhibitor

1y1n - MtMet-AP+K

3fm3 – EncMet-AP – Encephalitozoon cuniculi

3fmq, 3fmr - EncMet-AP+angiogenesis inhibitor

3d27, 2q92, 2q93, 2q94, 2q95, 2q96, 2p98, 2p99, 2p9a, 2gu4, 2gu5, 2gu6, 2evc, 2evm, 2evo, 2bbv, 1xnz – EcMet-AP+Mn+inhibitor

2gg0, 2gg2, 2gg3, 2gg5, 2gg7, 2gg8, 2gg9, 2ggb, 2ggc - EcMet-AP+Co+inhibitor

1c21, 1c22, 1c23, 1c24 - EcMet-AP +Co + methionine derivative

1c27 - EcMet-AP +Co +norleucine

2ea2, 2ea4, 2ga2, 2nq6, 2nq7, 1yw7, 1yw8, 1yw9 - hMet-AP+Mn+inhibitor

2gtx, 2gu7 – EcMet-AP

1yvm – EcMet-AP (mutant)+Co+thiabendazole

1mat – EcMet-AP+Co

2mat, 4mat - EcMet-AP (mutant)+Co

3mat - EcMet-AP (mutant)+Co+bestatin derivative

2b3h, 2b3k - hMet-AP+Co

1boa - hMet-AP+Co+ angiogenesis inhibitor

2b3l – hMet-AP

1kq0, 1kq9 – hMet-AP+methionine

2gz5, 2adu, 1qzy, 1b59, 1b6a, 1bn5 – hMet-AP+Co+inhibitor

1r58, 1r5g, 1r5h - hMet-AP+Mn+inhibitor

2g6p - hMet-AP truncated+Mn+inhibitor

1qxw, 1qxy, 1qxz – Met-AP+Co+inhibitor - Staphylococcus aureus

1o0x – TmMet-AP

Aspartic acid aminopeptidase
3l6s – hAsp-AP+aspartic hydroxamate

Asparagine aminopeptidase
3c17, 2zak – EcAsn-AP (mutant)

2zal – EcAsn-AP+Asp

2gez – Asn-AP – Lupinus luteus

Serine aminopeptidase
1b65 – Ser-AP – Ochrobactrum anthropi

Cytosolic aminopeptidase
3pei – Cyt-AP – Francisella tularensis

3kzw – Cyt-AP – Staphylococcus aureus

3ij3 – Cyt-AP – Coxiella burnetii

Aminopeptidase N
3ked – EcAPN+2,4-diaminobutyric acid – Escherichia coli

2hpo, 2dq6 – EcAPN

2hpt, 2dqm – EcAPN+bestatin

2zxg – EcAPN+transition state analog

3b2p, 3b2x, 3b34, 3b37, 3b3b – EcAPN+amino acid

2gtq – APN – Neisseria meningitides

Non-specific aminopeptidase
2ek8 – AnAP – Aneurinibacillus

2ek9 – AnAP+bestatin

1y0r, 1xfo – PhAP

1y0y – PhAP+amastatin

1amp - VpAP

1cp6, 1igb – VpAP+inhibitor

Cold-activated aminopeptidase
3cia – Col-AP – Colwellia psychrerythraea

Deblocking aminopeptidase
2gre – DAP – Bacillus cereus

Heat stable aminopeptidase
2ayi – AmpT – Thermus thermophilus

Aminopeptidase from Staphylococcus aureus
1zjc - AmpS

Metalloaminopeptidase
3q43, 3q44 – PfPFAP (mutant) + bestatin derivative

Stereomyces griesus aminopeptidase
1xjo, 1cp7 - SGAP

1qq9, 1f2o, 1f2p, 1tf8, 1tf9, 1tkf, 1tkh, 1tkj, 1xbu - SGAP + amino acid

S. griseus aminopeptidase


S. griseus aminopeptidase (SGAP) cleaves the N-terminal amino acid from a peptide or protein, and is specific for larger hydrophobic acids, especially leucine. No cleavage occurs if the next residue is proline.

The active site of the enzyme contains two Zn2+ ions with His85 and Asp160 as ligands for one ion, and Glu132 and His247 as ligands for the second ion. Asp97 is a common ligand to both ions. What appears to be a phosphate anion is bound to both zinc atoms, replacing the water molecule/hydroxide ion normally found in this class of enzyme.

Additional Resources
For additional information, see:

Amino Acid Synthesis & Metabolism

Streptomyces griseus Aminopeptidase (SGAP)